Comparison of 2 Immunomodulator Withdrawal Schemes for Infliximab Monotherapy in Active Pediatric Crohn's Disease After Thiopurine Failure

• Status: Terminated
• Trial end date: 2015-12-01
• Target enrollment: 0
• Participant gender: All

Summary

The goal of the present study is to evaluate the best regimen for infliximab monotherapy, and to evaluate if limited combination therapy with IFX and an Immunomodulator for the first 6 months of therapy, in prior Immunomodulator failures, is superior to monotherapy with Immunomodulator cessation from the second infusion, in preventing loss of remission to IFX.

• Phase: Phase 4
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: Prof. Arie Levine
• Treatments: 6-Mercaptopurine; Adjuvants, Immunologic; Azathioprine; Immunologic Factors; Infliximab; Mercaptopurine; Methotrexate

Criteria

Inclusion Criteria:

1. Crohns disease

2. Age: 6 - 18 years ( inclusive)

3. Active disease PCDAI >10, or any steroid dependence despite thiopurine use for >10 weeks.

4. Naïve to biologics

5. Informed consent

6. CRP ≥0.6 mg/dl

7. Neg. TB-Test, negative HBV- S Ag

8. Use of IMM at present or in past for at least 10 weeks ( for Withdraw only).

9. Negative stool culture, parasites and clostridium toxin current flare

Inclusion criteria Comments:

1. Patients receiving corticosteroids may be included if the disease is active and CRP elevated.

2. All other treatments such as 5ASA , , must be discontinued immediately after the first IFX infusion.

3. Patients may receive an antihistamine prior to any infusion.Use of corticosteroid pretreatment is allowed only during the first two infusions (single infusion on day of infliximab), or if an infusion reaction has occurred.

4. Partial enteral nutrition, accounting for less than 50% of daily required calories, may be supplied as needed.

5. Patients receiving antibiotics must cease use of antibiotics within the 14 days of receiving the first infusion.

6. ESR >20 can be alternative if the CRP <0.6.

7. Negative stool culture, parasites and clostridium toxin current flare will examined only if the patient has diarrhea.

8. Patients may be enrolled directly in to the Predict study , in which case duration of IMM is irrelevant , but patients must have received an IMM until week 2 as in the withdraw

Exclusion Criteria:

1. Intolerance to thiopurines/methotrexate

2. Pregnancy

3. Contraindication for any of the drugs.

4. Leukopenia <4000 or absolute neutrophil count below 1200 on two consecutive tests during screening.

5. Hepatocellular Liver disease ( ALT > 60 ) or cirrhosis.

6. Renal Failure

7. Prior idiosyncratic side effects with thiopurines ( pancreatitis etc).

8. Current abscess ( < 14 days of antibiotics) or perforation of the bowel( <14 days antibiotics).

9. Small bowel obstruction within the last 3 months

10. Fixed non inflammatory stricture with predilatation with symptoms related to stricture

11. Complicated or heavily draining perianal fistula ( indolent non draining or scant draining fistula are not exclusion criteria)

12. Prior treatment with infliximab

13. Previous malignancy

14. Toxic Megacolon

15. Sepsis

16. Surgery related to Crohn's disease in previous 8 weeks.

17. Positive Hepatitis B surface antigen or evidence for TB.

18. Current bacterial infection

19. IBD unclassified

Exclusion criteria Comments:

1. Prior surgery or post operative recurrence are not exclusion criteria.